1. Field of the Invention
The invention relates to N-unsubstituted amidinium salts, to precursors thereof and to a process for their preparation.
2. Brief Description of the Prior Art
N-unsubstituted amidines and their salts, called amidines and amidinium salts for simplicity hereinafter, are valuable synthons in the preparation of heterocyclic compounds. Such compounds have diverse applications in particular in the drugs sector and in crop protection. For example, vitamin B1, eprosartan and conivaptan can advantageously be prepared from alkylamidines or alkylamidinium salts.
Alkylamidinium salts such as, for example, acetamidinium chloride are prepared industrially by the so-called Pinner synthesis (Organic Synthesis Col. Vol. I, S: 4; RO 59061; Izobreteniya 1995(32), 264). This entails initial synthesis of the corresponding imidic ester hydrochloride from acetonitrile, methanol and HCl.
In the literature, the term imidic ester is also frequently referred to as imido ester, imino ester, imido ether, imidate or imino ether, but these are equivalent.
In a second step, the imidic ester hydrochloride, which is sparingly soluble and is therefore isolated as intermediate, is metered with a metering screw into an ammonia solution. This results in the acetamidine hydrochloride, which is likewise sparingly soluble. The described process has the disadvantage that, because of the great hygroscopicity and thermal instability of the intermediate, and its use as solid, special technical precautions are necessary to avoid losses. For the same reasons, handling of the solid acetamidine hydrochloride is not advantageous either.
These disadvantages can, according to JP-A-60-84254, be avoided if acetonitrile and hydrogen chloride are reacted together in a particular ratio. Use of 1.35 to 2 equivalents of hydrogen chloride results in a suspension, while a solution is obtained with more than 2 equivalents. This excess acid must, however, be very carefully neutralized before the reaction with ammonia in order to avoid overheating and the thermal decomposition mentioned previously. This measure means an additional reaction step and the formation of unwanted quantities of salt and is therefore not advantageous for industrial implementation.
There was thus a need to develop an industrially utilizable process for preparing amidines and amidinium salts which very substantially avoids additional neutralization steps or the technically elaborate intermediate isolation of sparingly soluble imidic ester salts.